Experimental lung research
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Adenosine (AD) has been reported to induce both pulmonary arterial constriction and dilation. We investigated the effect of AD using two complementary techniques. The isolated rat lung perfused with Earle's balanced salt solution containing albumin was used to measure pulmonary arterial (Ppa), venous, and double occlusion (microvascular; Pmv) pressure, and resistance changes. ⋯ In vessels without endothelium, only relaxation was observed. Isolated guinea pig arterial rings responded to AD with vasodilation similar to the results in the rat arterial rings. Results of this study show that AD primarily causes a direct dose-dependent relaxation of pulmonary arterial smooth muscle in both the isolated perfused lung and isolated arterial ring preparation.
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Verapamil, a calcium channel blocker has been used with partial success in cases of primary pulmonary hypertension, as well as to reduce hypoxia-induced pulmonary hypertension (PH) in rats. However, its effect on monocrotaline (MCT)-induced PH in rats is not known. We studied the effect of verapamil on MCT-induced PH. ⋯ Smaller pulmonary arteries (less than 150 microns in diameter) in MCT + VP-treated rats showed less medial thickening than MCT groups. However, diminished lung angiotensin-converting enzyme activity suggestive of endothelial cell dysfunction was noted in both MCT and MCT + VP-treated rats. This study indicates that verapamil attenuates MCT-induced PH, but has no effect on pulmonary endothelial cell dysfunction.
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The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils and macrophages in bronchoalveolar lavage (BAL) fluid. Interleukin-1 (IL-1), an inflammatory mediator produced by macrophages, has been shown to be chemotactic for neutrophils and to stimulate lymphocyte activation and proliferation of fibroblasts. BAL was performed in patients with ARDS, patients at high risk to develop ARDS, and in normal nonsmokers. ⋯ There was a correlation (r = 0.64, p less than .001) between IL-1 levels and BAL protein concentration. BAL IL-1 levels were highest in patients with the fully developed syndrome but were also elevated in patients at high risk. The absence of significant amounts of IL-1 in serum suggests that it may be produced within the lung.
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We studied changes in lung ultrastructure and collagen content during the repair of acute lung injury in adult rats exposed to 100% O2 for 60 h and recovering in ambient air. In the interstitium, during the first 3 days of repair, the number of neutrophils decreased 16-fold, and monocytes and lymphocytes increased to 7-fold and 4-fold the respective control values. Myofibroblasts increased about 5-fold and the volume of the interstitial matrix remained high. ⋯ In the epithelium, type 2 cells increased 150% during the first 3 days of repair before decreasing; type 1 cell number did not change. After 28 days of repair, the lungs appeared qualitatively almost normal; however, interstitial cell number and collagen content were still increased. We conclude that the repair of oxygen-induced lung injury involves a complex pattern of morphologic changes that has important similarities to those occurring during repair on other tissues such as the skin.
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Comparative Study
A quantitative study of the development of interalveolar pores in the postnatal mouse.
Quantitative analysis of regional interalveolar pore development in the lungs of C3Hf/He mice was performed using scanning electron microscopy. Lungs of male mice ages 7, 10, 14, 21, 28, and 56 days were studied following intratracheal fixation. Interalveolar pores were counted in subpleural, midzonal, and peribronchiolar regions. ⋯ The number of interalveolar pores increased 2-3 fold from ages 21 to 56 days. By age 28 days and thereafter interalveolar pores were more numerous in subpleural alveoli than in midzonal or peribronchiolar alveoli. We conclude that interalveolar pores appear diffusely in the lungs of mice during the third postnatal week and that regional differences in the number of interalveolar pores are established by age 28 days.